Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

In silico elucidation of potential drug target sites of the Thumb Index Fold Protein, Wnt-8b

Sheikh Arslan Sehgal^1-3 , Sonia Kanwal², Rana Adnan Tahir^2-4, Zunera Khalid², Mirza A Hammad^3,5

¹State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; ²Department of Biosciences, COMSATS Institute of Information Technology, Sahiwal, Pakistan; ³University of Chinese Academy of Sciences, Beijing, China; ⁴Beijing Key Laboratory of Separation and Analysis in Biomedical and Pharmaceuticals, Department of Biomedical Engineering, School of Life Sciences, Beijing Institute of Technology; ⁵National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

For correspondence:- Sheikh Sehgal Email: arslansehgal@yahoo.com

Accepted: 20 January 2018 Published: 31 March 2018

Citation: Sehgal SA, Kanwal S, Tahir RA, Khalid Z, Hammad MA. In silico elucidation of potential drug target sites of the Thumb Index Fold Protein, Wnt-8b. Trop J Pharm Res 2018; 17(3):491-497 doi: 10.4314/tjpr.v17i3.15

© 2018 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: The involvement of Wnt-8b in Wnt signaling pathway leads to various cancers. The purpose of this study was to determine the therapeutic compounds from the available library by targeting Wnt-8b using molecular docking analyses.

Methods: Threading and comparative modeling approaches were employed to predict the 3D structure of Wnt-8b. Sixty-eight models were evaluated using molprobity, ERRAT and rampage evaluation tools and the model having 82.456 % overall quality value was selected for further analyses. The acyl group was added to the suitable model to satisfy the hydrophobic nature of the Wnt-8b. Literature-derived compounds were selected for comparative molecular docking studies using GOLD, AutoDock and AutoDock Vina. Furthermore, docked complexes were analyzed and visualized using Chimera and Ligplot.

Results: The compound ZINC04029462 exhibited high binding potential with Wnt-8b and palmitoleic acid and was found common among top 20 compounds of each tool. His-183, Val-185, Ser-186, Gly-187, Ser-188 and Thr-190 residues commonly interacted with compounds and palmitoleic acid and considered as potential interacting residues.

Conclusion: Common interacting residues from top 20 compounds of each tool suggest that these compounds may be utilized to inhibit aberrant expression of Wnt-8b. The common inhibitor ZINC04029462 may act as a lead compound for further drug designing against Wnt family

Keywords: Wnt-8b, Cancer, Homology modeling, Molecular docking, AutoDock